title: Toxicological aspects of injectable gold-hyaluronan combination as a treatment for neuroinflammation.
abstract: Secondary inflammatory reactions to stroke or trauma contribute to irreplaceable loss of brain tissue of the affected patients. Likewise, neuroinflammatory processes are the main pathophysiological feature in Multiple Sclerosis (MS), a common neurodegenerative disease among young adults. In the search for safe and efficient ways to reduce inflammation within nervous tissue older immunosuppressive remedies have been re-investigated. The anti-inflammatory properties of gold salts are well known but result in uncontrollable systemic spread of gold ions, generating side effects such as nephrotoxicity, limiting their use. Recent studies have circumvented this obstacle by introducing metallic gold implants as a localized source of immune-modulating gold ions and suspension in hyaluronic acid (HA) enables injection of small amounts of gold in the natural spaces of the brain. By injecting >25 μm gold beads in HA intracerebrally we recently showed a slowing of disease progression in a rodent model of MS. The toxicological aspects were, however, not assessed. The present study investigates the viability of neuronal and macrophage cell cultures exposed to the gold/HA combination and the possible risk associated with unilateral gold/HA injection in young Balb/CA mice in the first 7 to 21 days of gold-exposure. Tracing by autometallography of gold accumulations throughout the brain exhibited sparse gold uptake in glia and neurons of hippocampus and cortex, and striatum and cerebellum were void of staining. No systemic spread of gold was seen in liver or kidney, nor were there signs of obstruction of the ventricular system. Both cell cultures of J774 macrophages and CCL neurons accumulated gold from gold/HA-exposure with no signs of reduced viability. In conclusion, our findings indicate that gold/HA is not overtly neuro- or cytotoxic, nor does intraventricular exposure result in widespread gold accumulation or tissue damage, warranting further studies into the pharmacological properties of this novel form of gold treatment.
authors.affiliation: Department of Biomedicine - Pharmacology, Aarhus University, Denmark. dspe@farm.au.dk.
authors.forename: Dan Sonne
authors.initials: DS
authors.lastname: Pedersen
authors.affiliation: Department of Biomedicine - Anatomy, Aarhus University, Denmark.
authors.forename: Linda J
authors.initials: LJ
authors.lastname: Locht
authors.affiliation: Department of Biomedicine - Pharmacology, Aarhus University, Denmark.
authors.forename: Thao P
authors.initials: TP
authors.lastname: Tran
authors.affiliation: Department of Biomedicine - Anatomy, Aarhus University, Denmark.
authors.forename: Sara
authors.initials: S
authors.lastname: Markholt
authors.affiliation: Department of Biomedicine - Pharmacology, Aarhus University, Denmark.
authors.forename: Jørgen
authors.initials: J
authors.lastname: Rungby
authors.affiliation: Department of Biomedicine - Pharmacology, Aarhus University, Denmark.
authors.forename: Agnete
authors.initials: A
authors.lastname: Larsen
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000378:metabolism / Q000633:toxicity*; D001921:Brain / Q000187:drug effects*; D002460:Cell Line; D005260:Female; D017612:Gold Compounds / Q000378:metabolism / Q000633:toxicity*; D006820:Hyaluronic Acid / Q000378:metabolism / Q000633:toxicity*; D007249:Inflammation / Q000188:drug therapy; D008807:Mice, Inbred BALB C; D009474:Neurons / Q000187:drug effects*
chemical_list: D000893:Anti-Inflammatory Agents; D017612:Gold Compounds; D006820:Hyaluronic Acid